ADAM9 functions as a promoter of gastric cancer growth which is negatively and post-transcriptionally regulated by miR-126

Wang, Junqing; Zhou, Yunyun; Fei, Xiaochun; Chen, Xuehua; Yan, Jiqi; Liu, Bingya; Zhu, Zhenggang

doi:10.3892/or.2017.5460

Cited by 26 publications

(17 citation statements)

References 30 publications

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“…In addition, using RNA-seq based transcriptome profiling we compared down-regulated genes with in silico target prediction and identified 10 candidate genes. Interestingly, results from literature research showed that 6 of the genes ( ADAM9, PLK2, CAMSAP1, PTPN9, EGFL7 and SLC7A5 ) have been demonstrated as the functional targets of miR-126 (23, 34–42), suggesting the relevance of our analysis. To identify the GCT-relevant target of miR-126, we screened all the 10 candidate genes in KGN cells by RNAi.…”

Section: Discussionmentioning

confidence: 85%

microRNA-126 Is a Tumor Suppressor of Granulosa Cell Tumor Mediated by Its Host Gene EGFL7

Cheung

Lü

et al. 2019

Front. Oncol.

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MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression at a post-transcriptional level. We examined the role of miR-126 in granulosa cell tumor (GCT) of the ovaries. In tissues from malignant GCT patients miR-126 expression was repressed. We showed that miR-126 could inhibit proliferation, migration, hormone production and promote apoptosis of cancerous granulosa cells (GCs) in vitro . The role of miR-126 as “tumor suppressor” was confirmed by using a tumor formation model in vivo . By RNA-seq, immunohistochemical staining (IHC), Western blot and luciferase reporter assay, we identified and confirmed EGFL7 as a direct functional target of miR-126 in cancer GCs. Furthermore, we found that the AKT signaling pathway was associated with miR-126 and EGFL7 in cancer GCs. Taken together, our results demonstrate a function of miR-126 in the suppression of GCT development via the regulation of EGFL7.

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Section: Discussionmentioning

confidence: 85%

microRNA-126 Is a Tumor Suppressor of Granulosa Cell Tumor Mediated by Its Host Gene EGFL7

Cheung

Lü

et al. 2019

Front. Oncol.

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“…The roles of ADAM9 in different types of cancers have been discussed in many previous works. Caporali et al suggested that microRNA‐126‐3p may contribute to the dabrafenib resistance of melanoma via up‐regulating ADAM9 Caporali; Oria et al found that ADAM9 may contribute to the development of pancreatic ductal adenocarcinoma; Dong et al demonstrated that ADAM9 can induce the epithelial‐mesenchymal transition of the hepatoma cells; Wang et al suggested that ADAM9 functions as an oncogene in gastric cancer, and it was negatively regulated by micoRNA‐126 . A study on the roles of ADAM9 in OC is limited.…”

Section: Discussionmentioning

confidence: 99%

“…A disintegrin and metalloproteinase 9 is a member of the ADAM families, and the roles of ADAM9 in different types of cancers have been discussed previously. [12][13][14] In the case of OC, ADAM9 was found to be up-regulated in tumor tissue than the normal tissue 15 ; however, the underlying mechanism is still unclear. In the present study, we will examine expression of ADAM9 in human OC tissue by immunohistochemistry and RT-qPCR method and investigate potential diagnostic and prognostic value of ADAM9 for OC.…”

Section: Introductionmentioning

confidence: 99%

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Aberrant expression of ADAM9 in ovarian cancer and its clinical significance

Guo

Yuan

et al. 2019

Clinical Laboratory Analysis

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Background:The oncogene a disintegrin and metalloproteinase 9 (ADAM9) was upregulated in ovarian cancer tissues, and the present study aims to explore the potential diagnostic and prognostic value of ADAM9 in ovarian cancer (OC). Methods:A total of 30 paired fresh OC tumor tissues and the paired-adjacent normal tissue, and 90 formalin-fixed paraffin-embedded (FFPE) OC samples and adjacent normal tissue were collected. The expression of OC in FFPE samples was examined by immunohistochemical methods, and the mRNA expression of ADAM9 in fresh tumor samples was examined by RT-qPCR methods. Receiver operating characteristics curve was drawn to analyze the potential diagnostic value of ADAM9. Kaplan-Meier survival analysis was performed to compare the overall survival (OS) and disease-free survival (DFS) of the ADAM9 positive and negative OC patients. Results:The positive rate of ADAM9 in FFPE OC tumor tissue was markedly higher than in the non-tumorous tissue (61/90 vs 47/90), and increased expression level of ADAM9 may associate with higher histological grade, advanced Figo stage and increased risk of metastasis; moreover, the mRNA expression of ADAM9 was also increased in OC tissue compared with the normal tissue (P < .001), and results of ROC analysis suggested that ADAM9 is a sensitive marker for the diagnosis of OC( AUC 0.8389, 95% confidence interval 0.7333 to 0.9445); finally, increased expression of ADAM9 may indicate decreased OS (P = .004) and DFS (P = .014) of the patients. Conclusion:A disintegrin and metalloproteinase 9 was up-regulated in OC, and ADAM9 may serve as potential diagnostic and prognostic marker for the diagnosis and treatment of OC. K E Y W O R D SA disintegrin and metalloproteinase 9, diagnosis, ovarian cancer, prognosisThis is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

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“…Located at chromosome 9q34.3, an intron of EGF-like domain-containing protein 7 (EGFL7), miRNA (miR)-126 is associated with various human tumors (19). Commonly exhibiting tumor suppressive properties, miR-126 is expressed at a low level in numerous human malignances, including lung cancer (20), colon cancer (21), breast cancer (22), osteosarcoma (23) and gastric cancer (24). Repression of cancer cell proliferation (25), migration (26) and invasion (27) mediated by miR-126 can be achieved via targeting specific oncogenes, including phospoinositide 3-kinase, V-Ki-ras2 Kirsten rat sarcoma viral oncogene, EGFL7 and vascular endothelial growth factor (VEGF).…”

Section: Introductionmentioning

confidence: 99%

PTPN9 promotes cell proliferation and invasion in Eca109 cells and is negatively regulated by microRNA-126

Zhu

et al. 2017

Oncology Letters

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Protein tyrosine phosphatase non-receptor type 9 (PTPN9), also named PTP-MEG2, is an important member of the protein tyrosine phosphatase family that is involved in variety of human diseases. However, the role of PTPN9 in esophageal squamous cell carcinoma (ESCC) remains to be established. The present evaluated the potential effect and underlying mechanism of action of PTPN9 in ESCC. Immunohistochemistry was performed to detect PTPN9 protein expression in 84 ESCC tumor specimens and 30 normal esophageal tissues. The association between positive expression of PTPN9 and clinicopathological features and prognosis was analyzed. The prognostic role of PTPN9 was further investigated using multivariate regression analysis. PTPN9-small interfering RNA and microRNA (miR-126)-mimics were transfected into Eca109 cells to construct PTPN9 silencing and an miR-126 ectopic expression cell model. Reverse transcription-quantitative polymerase chain reaction, western blot analysis, cell counting kit-8, Transwell assays and flow cytometry were used to investigate the role of PTPN9 in the process of ESCC progression and its potential downstream signaling pathway. Immunohistochemical analysis revealed that PTPN9 was upregulated in ESCC tumor specimens compared with normal esophageal tissues. The χ2 test indicated that positive expression of PTPN9 was correlated with tumor node metastasis stage, tumor classification and node classification. Patients with PTPN9 positive expression had shorter survival time, compared with those that were PTPN9 negative. Multivariate regression analysis with the Cox proportional hazards regression model revealed that PTPN9 expression was a prognostic factor of overall survival for patients with ESCC. Using RNA interference, the present study demonstrated that knockdown of PTPN9 significantly suppressed cell proliferation and invasion in Eca109. Additionally, it was hypothesized that miR-126, described as a tumor suppressor in ESCC, may act at least in part via its inhibition of PTPN9 at the post-transcriptional level. To the best of our knowledge, this is the first study to demonstrate that PTPN9 is overexpressed in ESCC and associated with poor survival, and may therefore be important in the pathogenesis of ESCC.

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ADAM9 functions as a promoter of gastric cancer growth which is negatively and post-transcriptionally regulated by miR-126

Cited by 26 publications

References 30 publications

microRNA-126 Is a Tumor Suppressor of Granulosa Cell Tumor Mediated by Its Host Gene EGFL7

microRNA-126 Is a Tumor Suppressor of Granulosa Cell Tumor Mediated by Its Host Gene EGFL7

Aberrant expression of ADAM9 in ovarian cancer and its clinical significance

PTPN9 promotes cell proliferation and invasion in Eca109 cells and is negatively regulated by microRNA-126

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